Known in the art (Kusumoto S., Tarumi Y., Ikenaka K., Shiba T., Bull. Chem. Soc. (Japan) 49, (2), 533-539 (1976); and Lefrancier P., Choay J., Derrien M., Lederman I., Int. J. Pept. Protein Res., 9, No. 4, 249-257 (1977) is synthesis of certain fragments and analogues of glycopeptides of cell walls of bacteria, namely N-acetylmuramylpeptides of the formula: ##STR3## wherein R is residues of aminoacids or peptides such as Ala, Gly, Ala-D-Glu, Ala-D-Glu-NH.sub.2, ##STR4## D-Ala-D-Glu-NH.sub.2 and the like.
The synthesis comprises condensation of benzyl esters of corresponding aminoacids or peptides with blocked N-acetylmuramic acid.
This prior art method for the preparation of said glycopeptides has a disadvantage residing in that into the condensation reaction only blocked N-acetylmuramic acid (benzyl-2-acetamido-4,6-benzylidene-3-O-/D-1'-carboxyethyl/-2-deoxy-.alpha .-D-glucopyranoside/ is introduced which is preliminary synthetized in three stages from N-acetylglucosamine with a yield of 17-22% following the below-given scheme: ##STR5##
Some of the above-mentioned synthetic N-acetylmuramylpeptides are strong adjuvants.
In a joint paper by Soviet and Bulgarian scientists Kotani S., Watanabe Y., Kinoshita F., Shimono T., Morisaki I., Shiba T., Kusumto S., Tarumi Y., Ikenaka K., Biken J. 18, 105 (1975)) it has been shown that a mixture of glycopeptides isolated from cell walls of Lactobacillus bulgarieus has an unusual antitumor activity: neutral glycopeptides of Lactobacillus bulgarieus cause necrosis of the tumor tissue on mice with sarcoma S-180 (Bogdanov I. G., Dalev P. G., Gurevich A. I., Kolosov M. N., Malkova V. P., Plemyannikova L. A., Sorokina I. B., Febs. Letters 57, No. 3, 259 (1975)). The synthesis of these glycopeptides is hitherto unknown.
The detection of biological activity (adjuvant activity and ability to cause necrosis in a tumor tissue) of glycopeptides isolated from cell walls of bacteria has given impetus to a synthetic preparation of various fragments of naturally-occurring glycopeptides and analogues thereof necessary for a profound investigation of biological activity of these compounds.
Analysis of fragments of glycopeptides isolated from cell walls of different microorganisms and demonstrating adjuvant activity, as well as analysis of glycopeptides of Lactobacillus bulgarieus revealing an unusual antitumor activity has shown that both N-acetylmuramic acid and N-acetyl-glucosamine are incorporated in the sugar part of the molecules of glycopeptides. However, the synthesis of glycopeptides containing, apart from N-acetylmuramic acid, N-acetylglucosamine, i.e. the synthesis of N-acetylglucosaminyl-N-acetylmuramylpeptides has not been hitherto known from the literature. The prior art method for the synthesis of said muramylpeptides makes it possible to obtain only N-acetylmuramylpeptides. The multi-stage synthesis scheme employed for this purpose is unsuitable in principle for association of the residue of N-acetylglucosamine with N-acetylmuramic acid by means of the bond 1.fwdarw.4 (all residues of aminosugars in any glycopeptide of cell walls of bacteria are interconnected by the bond 1.fwdarw.4). Therefore, the known method for preparing N-acetylmuramylpeptides cannot be used for the synthesis of N-acetylglucosaminyl-/1.fwdarw.4/-N-acetyl muramylpeptides. This defined the attempts in finding a new method for the preparation of various fragments and analogues of naturally-occurring glycopeptides of cell walls of bacteria.